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将碳酸酐酶和硫氧还蛋白还原酶抑制基序结合在单个分子中会显著增加其细胞毒性。

Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity.

机构信息

Saint Petersburg State University, Saint Petersburg, Russian Federation.

Latvian Institute of Organic Synthesis, Riga, Latvia.

出版信息

J Enzyme Inhib Med Chem. 2020 Dec;35(1):665-671. doi: 10.1080/14756366.2020.1734800.

DOI:10.1080/14756366.2020.1734800
PMID:32131646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7067156/
Abstract

A hypothesis that simultaneous targeting cancer-related carbonic anhydrase CA IX and CA XII isoforms (whose overexpression is a cancer cell's defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

摘要

一种假说认为，同时针对与癌症相关的碳酸酐酶 CAIX 和 CA XII 同工型（其过表达是癌细胞对缺氧的防御机制）以及硫氧还蛋白还原酶（在癌症中过表达以抵御氧化应激），可能会导致协同的抗增殖作用。这一假说通过测试两种抑制剂类别对胰腺癌细胞（PANC-1）的组合得到了证实。将两种药效团在一个分子内结合，导致细胞毒性急剧增加。这一初步观察为抗癌药物设计的一种全新方法奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/0720fae86c3b/IENZ_A_1734800_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/c1a7922f57a7/IENZ_A_1734800_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/c22beac0c17d/IENZ_A_1734800_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/71b58ea79fca/IENZ_A_1734800_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/6a98233f164f/IENZ_A_1734800_SCH0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/162b685091d5/IENZ_A_1734800_SCH0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/9bcfe5ad9fac/IENZ_A_1734800_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/0b811e9d2646/IENZ_A_1734800_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/0720fae86c3b/IENZ_A_1734800_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/c1a7922f57a7/IENZ_A_1734800_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/c22beac0c17d/IENZ_A_1734800_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/71b58ea79fca/IENZ_A_1734800_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/6a98233f164f/IENZ_A_1734800_SCH0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/162b685091d5/IENZ_A_1734800_SCH0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/9bcfe5ad9fac/IENZ_A_1734800_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/0b811e9d2646/IENZ_A_1734800_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4525/7067156/0720fae86c3b/IENZ_A_1734800_F0003_B.jpg

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